Monthly Archives: June 2015

A demonstration against World No Tobacco Day in Jakarta, Indonesia, in 2013. The U.S. Chamber of Commerce and its foreign affiliates have joined efforts to fight antismoking laws around the world.Credit Romeo Gacad/Agence France-Presse — Getty Images

KIEV, Ukraine — A parliamentary hearing was convened here in March to consider an odd remnant of Ukraine’s corrupt, pre-revolutionary government.

Three years ago, Ukraine filed an international legal challenge against Australia, over Australia’s right to enact antismoking laws on its own soil. To a number of lawmakers, the case seemed absurd, and they wanted to investigate why it was even being pursued.

When it came time to defend the tobacco industry, a man named Taras Kachka spoke up. He argued that several “fantastic tobacco companies” had bought up Soviet-era factories and modernized them, and now they were exporting tobacco to many other countries. It was in Ukraine’s national interest, he said, to support investors in the country, even though they do not sell tobacco to Australia.

Mr. Kachka was not a tobacco lobbyist or farmer or factory owner. He was the head of a Ukrainian affiliate of the U.S. Chamber of Commerce, America’s largest trade group.

From Ukraine to Uruguay, Moldova to the Philippines, the U.S. Chamber of Commerce and its foreign affiliates have become the hammer for the tobacco industry, engaging in a worldwide effort to fight antismoking laws of all kinds, according to interviews with government ministers, lobbyists, lawmakers and public health groups in Asia, Europe, Latin America and the United States.

The U.S. Chamber’s work in support of the tobacco industry in recent years has emerged as a priority at the same time the industry has faced one of the most serious threats in its history. A global treaty, negotiated through the World Health Organization, mandates anti-smoking measures and also seeks to curb the influence of the tobacco industry in policy making. The treaty, which took effect in 2005, has been ratified by 179 countries; holdouts include Cuba, Haiti and the United States.

Facing a wave of new legislation around the world, the tobacco lobby has turned for help to the U.S. Chamber of Commerce, with the weight of American business behind it. While the chamber’s global tobacco lobbying has been largely hidden from public view, its influence has been widely felt.

Letters, emails and other documents from foreign governments, the chamber’s affiliates and antismoking groups, which were reviewed by The New York Times, show how the chamber has embraced the challenge, undertaking a three-pronged strategy in its global campaign to advance the interests of the tobacco industry.

In the capitals of far-flung nations, the chamber lobbies alongside its foreign affiliates to beat back antismoking laws.

In trade forums, the chamber pits countries against one another. The Ukrainian prime minister, Arseniy Yatsenyuk, recently revealed that his country’s case against Australia was prompted by a complaint from the U.S. Chamber.

And in Washington, Thomas J. Donohue, the chief executive of the chamber, has personally taken part in lobbying to defend the ability of the tobacco industry to sue under future international treaties, notably the Trans-Pacific Partnership, a trade agreement being negotiated between the United States and several Pacific Rim nations.

“They represent the interests of the tobacco industry,” said Dr. Vera Luiza da Costa e Silva, the head of the Secretariat that oversees the W.H.O treaty, called the Framework Convention on Tobacco Control. “They are putting their feet everywhere where there are stronger regulations coming up.”

Thomas J. Donohue, the head of the U.S. Chamber of Commerce, has defended the tobacco industry’s right to sue under future international treaties.Credit Brendan Hoffman for The New York Times

The increasing global advocacy highlights the chamber’s enduring ties to the tobacco industry, which in years past centered on American regulation of cigarettes. A top executive at the tobacco giant Altria Group serves on the chamber’s board. Philip Morris International plays a leading role in the global campaign; one executive drafted a position paper used by a chamber affiliate in Brussels, while another accompanied a chamber executive to a meeting with the Philippine ambassador in Washington to lobby against a cigarette-tax increase. The cigarette makers’ payments to the chamber are not disclosed.

It is not clear how the chamber’s campaign reflects the interests of its broader membership, which includes technology companies like Google, pharmaceutical giants like Pfizer and health insurers like Anthem. And the chamber’s record in its tobacco fight is mixed, often leaving American business as the face of a losing cause, pushing a well-known toxin on poor populations whose leaders are determined to curb smoking.

The U.S. Chamber issued brief statements in response to inquiries. “The Chamber regularly reaches out to governments around the world to urge them to avoid measures that discriminate against particular companies or industries, undermine their trademarks or brands, or destroy their intellectual property,” the statement said, adding, “we’ve worked with a broad array of business organizations at home and abroad to defend these principles.”

The chamber declined to say if it supported any measures to curb smoking.

The chamber, a private nonprofit that has more than three million members and annual revenue of $165 million, spends more on lobbying than any other interest group in America. For decades, it has taken positions aimed at bolstering its members’ fortunes.

While the chamber has local outposts across the United States, it also has more than 100 affiliates around the world. Foreign branches pay dues and typically hew to the U.S. Chamber’s strategy, often advancing it on the ground. Members include both American and foreign businesses, a symbiotic relationship that magnifies the chamber’s clout.

For foreign companies, membership comes with “access to the U.S. Embassy” according to the Cambodian branch, and entree to “the U.S. government,” according to the Azerbaijan branch. Members in Hanoi get an invitation to an annual trip to “lobby Congress and the administration” in Washington.

Since Mr. Donohue took over in 1997, he has steered the chamber into positions that have alienated some members. In 2009, the chamber threatened to sue if the Environmental Protection Agency regulated greenhouse gas emissions, disputing its authority to act on climate change. That led Nike to step down from the chamber’s board, and to Apple’s departure from the group. In 2013, the American arm of the Swedish construction giant Skanska resigned, protesting the chamber’s support for what Skanska called a “chemical industry-led initiative” to lobby against green building codes.

The chamber’s tobacco lobbying has led to confusion for many countries, Dr. da Costa e Silva said, adding “there is a misconception that the American chamber of commerce represents the government of the U.S.” In some places like Estonia, the lines are blurred. The United States ambassador there, Jeffrey Levine, serves as honorary president of the chamber’s local affiliate; the affiliate quoted Philip Morris in a publication outlining its priorities.

The tobacco industry has increasingly turned to international courts to challenge antismoking laws that countries have enacted after the passage of the W.H.O. treaty. Early this year, Michael R. Bloomberg and Bill Gates set up an international fund to fight such suits. Matthew L. Myers, president of the Campaign for Tobacco-Free Kids, an advocacy group that administers the fund, called the chamber “the tobacco industry’s most formidable front group,” adding, “it pops up everywhere.”

In Ukraine, the chamber’s involvement was no surprise to Hanna Hopko, the lawmaker who led the hearing in Parliament. She said the chamber there had fought against antismoking laws for years.

“They were against the tobacco tax increase, they were against placing warning labels on cigarettes,” she said. “This is just business as usual for them.”

Plain packaged tobacco products with health warnings in Sydney, Australia.Credit Andrew Quilty for The New York Times

Country-by-Country Strategy

More than 3,000 miles away, in Nepal, the health ministry proposed a law last year to increase the size of graphic warning labels from covering three-fourths of a cigarette pack to 90 percent. Countries like Nepal that have ratified the W.H.O. treaty are supposed to take steps to make cigarette packs less appealing.

Not long afterward, one of Nepal’s top officials, Lilamani Poudel, said he received an email from a representative of the chamber’s local affiliate in the country, warning that the proposal “would negate foreign investment” and “invite instability.”

In January, the U.S. Chamber itself weighed in. In a letter to Nepal’s deputy prime minister, a senior vice president at the chamber, Tami Overby, wrote that she was “not aware of any science-based evidence” that larger warning labels “will have any discernible impact on reducing or discouraging tobacco use.”

A 2013 Harvard study found that graphic warning labels “play a lifesaving role in highlighting the dangers of smoking and encouraging smokers to quit.”

While Nepal eventually mandated the change in warning labels, cigarette companies filed for an extension and compliance has stalled.

“Since we have to focus on responding to the devastating earthquake, we have not been able to monitor the state of law enforcement effectively,” said Shanta Bahadur Shrestha, a senior health ministry official.

The episode reflects the chamber’s country-by-country lobbying strategy. A pattern emerged in letters to seven nations: Written by either the chamber’s top international executive, Myron Brilliant, or his deputies, they introduced the chamber as “the world’s largest business federation.”

Then the letters mention a matter “of concern.” In Jamaica and Nepal, it was graphic health warnings on packages. In Uruguay, it was a plan to bar cigarettes from being displayed by retailers. The Moldovan president was warned against “extreme measures” in his country, though they included common steps like restricting smoking in public places and banning advertising where cigarettes are sold.

A proposal to raise cigarette taxes in the Philippines would open the floodgates to smugglers, the government there was told. Tax revenue has increased since the proposal became law.

“We are not cowed by them,” said Jeremias Paul, the country’s under secretary of finance. “We meet with these guys when we’re trying to encourage investment in the Philippines, so clearly they are very influential, but that doesn’t mean they will dictate their ways.”

Protecting tobacco companies is portrayed by the chamber as vital for a nation’s economic health. Uruguay’s president is warned that antismoking laws will “have a disruptive effect on the formal economy.” El Salvador’s vice president is told that “arbitrary actions” like requiring graphic health warnings in advertisements undermine “investment and economic growth.”

On the ground, the chamber’s local affiliates use hands-on tactics.

After Moldova’s health ministry proposed measures in 2013, Serghei Toncu, the head of the American Chamber of Commerce in Moldova, laid out his objections in a series of meetings held by a regulatory review panel.

“The consumption of alcohol and cigarettes is at the discretion of each person,” Mr. Toncu said at one meeting, adding that the discussion should not be about “whether smoking is harmful.”

“You do not respect us,” he told the health ministry at another.

At a third, he called the ministry’s research “flawed from the start.”

His objections were not merely plaintive cries. The American chamber has a seat on Moldova’s regulatory review panel giving it direct influence over policy making in the small country.

“The American Chamber of Commerce is a very powerful and active organization,” said Oleg Chelaru, a team leader on the staff that assists the review panel. “They played a very crucial role in analyzing and giving an opinion on this initiative.”

Mr. Toncu, who has since left the chamber, declined to comment. Mila Malairau, the chamber’s executive director, said its main objective was to make sure the industry “was consulted” in “a transparent and predictable manner.”

After recently passing in Parliament, the long-stalled measures were subject to fresh objections from the chamber and others, and have not yet been enacted.

Protesters displayed fake body bags at a tobacco trade show at Pasay, the Philippines, in 2013.Credit Bullit Marquez/Associated Press

Fighting a Trade Exception

In Washington, the U.S. Chamber’s tobacco lobbying has been visible in the negotiations over the Trans-Pacific Partnership, a priority of the Obama administration that recently received critical backing in Congress.

One of the more controversial proposals would expand the power of companies to sue countries if they violate trade rules. The U.S. Chamber has openly opposed plans to withhold such powers from tobacco companies, curbing their ability to challenge national antismoking laws. The chamber says on its website that “singling out tobacco” will “open a Pandora’s box as other governments go after their particular bêtes noires.”

The issue is still unresolved. A spokesman for the United States trade representative said negotiators would ensure that governments “can implement regulations to protect public health” while also “ensuring that our farmers are not discriminated against.”

Email traffic shows that Mr. Donohue, the chamber’s head, sought to raise the issue in 2012 directly with Ron Kirk, who was then the United States trade representative. In email exchanges between staff members of the two, Mr. Donohue specifically sought to discuss the role of tobacco in the trade agreement.

“Tom had a couple of things to raise, including urging that the tobacco text not be submitted at this round,” one of Mr. Donohue’s staff members wrote to Mr. Kirk’s staff. The emails were produced in response to a Freedom of Information request filed by the Campaign for Tobacco-Free Kids, which provided them to The Times.

Mr. Kirk is now a senior lawyer at Gibson, Dunn, a firm that counts the tobacco industry as a client. He said in an interview that during his tenure as trade representative, he met periodically with Mr. Donohue but could not recall a specific conversation on tobacco.

He said trade groups were generally concerned about “treating one industry different than you would treat anyone else, more so than doing tobacco’s bidding.”

The chamber declined to make Mr. Donohue available for an interview.

A Face-Saving Measure

In Ukraine, it was Valeriy Pyatnytskiy who signed off on the complaint against Australia in 2012, which was filed with the World Trade Organization. At the time, he was Ukraine’s chief negotiator to the W.T.O. His political career has survived the revolution and he is now an adviser to the Ukrainian prime minister, Mr. Yatsenyuk.

In a recent interview, he said that for Ukraine, the case was a matter of principle. It was about respecting the rules.

He offered a hypothetical: If Ukraine allowed Australia to use plain packaging on cigarettes, what would stop Ukraine from introducing plain packaging for wine? Then Ukrainian winemakers could better compete with French wines, because they would all be in plain bags marked red or white.

“We had this in the Soviet times,” he said. “It was absolutely plain packaging everywhere.”

Some Ukrainian officials have long been troubled by the case.

“It has nothing to do with trade laws,” said Pavlo Sheremeta, who briefly served as Ukraine’s economic minister after the revolution. “We have zero exports of tobacco to Australia, so what do we have to do with this?”

Last year, he urged the American Chamber in Kiev to reconsider.

“I wrote a formal letter, asking them, ‘Do you still keep the same position?’ ” Mr. Sheremeta said. “Basically I was suggesting a face-saving way out of this.” But when he met with chamber officials, the plain packaging case was outlined as a top priority.

They refused to back down. After Mr. Pyatnytskiy, a tobacco ally, was installed as his deputy, Mr. Sheremeta resigned.

“The world was laughing at us,” he said of the case.

Shortly after The Times discussed the case with Ukrainian government officials, there were new protests from activists. Mr. Yatsenyuk called for a review of the matter. Ukraine has since suspended its involvement, but other countries including Cuba and Honduras are continuing to pursue the case against Australia.

Andy Hunder, who took over as president of the American Chamber of Commerce in Kiev in April, said the organization was moving on, adding, “We are looking forward now.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Schematic showing the shedding of tumor DNA from head and neck cancers into the saliva or plasma. Tumors from various anatomic locations shed DNA fragments containing tumor-specific mutations and human papillomavirus DNA into the saliva or the circulation. The detectability of tumor DNA in the saliva varied with anatomic location of the tumor, with the highest sensitivity for oral cavity cancers. The detectability in plasma varied much less in regard to the tumor’s anatomic location. Credit: Wang et al., Science Translational Medicine (2015)

On the hunt for better cancer screening tests, Johns Hopkins scientists led a proof of principle study that successfully identified tumor DNA shed into the blood and saliva of 93 patients with head and neck cancer. A report on the findings is published in the June 24 issue of Science Translational Medicine.

“We have shown that tumor DNA in the blood or saliva can successfully be measured for these cancers,” says Nishant Agrawal, M.D., associate professor of otolaryngology—head and neck surgery—and of oncology at the Johns Hopkins University School of Medicine. “In our study, testing saliva seemed to be the best way to detect cancers in the oral cavity, and blood tests appeared to find more cancers in the larynx, hypopharynx and oropharynx. However, combining blood and saliva tests may offer the best chance of finding cancer in any of those regions.”

Agrawal explains that inborn genetic predispositions for most head and neck cancers are rare, but other mutations that don’t generally occur in normal cells have long been considered good targets for screening tests.

In the case of head and neck cancers associated with HPV—tumors on the rise among Americans—Agrawal and his colleagues searched patients’ blood and saliva samples for certain tumor-promoting, HPV-related DNA. For non-HPV-related cancers, which account for the worldwide majority of head and neck tumors, they looked for mutations in cancer-related genes that included TP53, PIK3CA, CDKN2A, FBXW7, HRAS and NRAS.

The major risk factors for head and neck cancers are alcohol, tobacco—including chewing tobacco—and HPV infection.

For the study, 93 patients with newly diagnosed and recurrent head and neck cancer gave saliva samples, and 47 of them also donated blood samples before their treatment at The Johns Hopkins Hospital and MD Anderson Cancer Center in Texas. The scientists detected tumor DNA in the saliva of 71 of the 93 patients (76 percent) and in the blood of 41 of the 47 (87 percent). In the 47 who gave blood and saliva samples, scientists were able to detect tumor DNA in at least one of the body fluids in 45 of them (96 percent).

When the scientists analyzed how well their tumor DNA tests found cancers in certain regions of the head and neck, they found that saliva tests fared better than blood tests for oral cavity cancers. All 46 oral cavity cancers were correctly identified through saliva tests, compared with 16 of 34 oropharynx cancers (47 percent), seven of 10 larynx cancers (70 percent) and two of three hypopharynx cancers (67 percent).

The oral cavity refers to areas within the mouth, including the lips, front of the tongue, cheeks and gums. The oropharynx and hypopharynx are located in the back of the throat. The larynx, also in the throat, is typically known as the voice box.

“One reason that saliva tests may not have been as effective for cancer sites in the back of the throat is because we didn’t ask patients to gargle; we only asked them to rinse their mouths to provide the samples,” says Agrawal, a member of Johns Hopkins’ Kimmel Cancer Center and Ludwig Center.

Agrawal says the sensitivity of the tests overall depended on the cancer site, stage and HPV status, ranging between 86 to 100 percent. He also reports that saliva tests performed better for early-stage cancers, finding all 20 cancers, compared with blood tests that correctly identified seven of 10. He and his team found the opposite was true for late-stage cancers: Blood tests found more late-stage cancers (34 of 37), compared with saliva tests (51 of 73). Blood tests also correctly identified HPV-related tumors, occurring in 30 of the 93 patients, more often than saliva tests, probably because HPV-related tumors tend to occur in the back of the throat, which may not have been reached with the saliva rinse.

“Our ultimate goal is to develop better screening tests to find head and neck cancers among the general population and improve how we monitor patients with cancer for recurrence of their disease,” says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins Kimmel Cancer Center, co-director of the Ludwig Center at Johns Hopkins and a co-author of the study.

The scientists caution that further study of their tumor DNA detection method in larger groups of patients and healthy people is needed before clinical effectiveness can be determined, and that refinements also may be needed in methods of collecting saliva and the range of cancer-specific genes in the gene test panel.

In addition, Agrawal says: “We don’t yet have definitive data on false positive rates, and won’t until there are more studies of the tests in healthy people.” However, he notes, the formulas used to analyze their blood and saliva tests are designed to weed out questionable results.

False results in gene tests arise when DNA are copied many times, sequenced and analyzed. The scientists used a method they developed and tested previously in cervical fluid to find ovarian and cervical cancers. Specifically, they attach a kind of genetic bar code—a random set of 14 DNA base pairs—to trace each copied DNA fragment to its original one. DNA copies lacking the bar code are suspected to be an artifact of the process, and any mutation found in it is disregarded.

Agrawal says that tests like the one his team used, if used commercially, likely would cost several hundred dollars, and “our long-term goal is to create a test that costs less than $50 so it can be administered by physicians or dentists.”

To screen for head and neck cancers, which occur in more than 50,000 people in the U.S. each year, doctors conduct physical examinations. Biopsies are taken of suspicious-looking lesions, but “this method is not ideal, as evidenced by the fact that most head and neck cancers are rarely found at very early stages, when they are most curable,” says Agrawal.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

The following is a script of “The Cost of Cancer Drugs” which aired on October 5, 2014, and was rebroadcast on June 21, 2015. Lesley Stahl is the correspondent. Richard Bonin, producer.

Cancer is so pervasive that it touches virtually every family in this country. More than one out of three Americans will be diagnosed with some form of it in their lifetime. And as anyone who’s been through it knows, the shock and anxiety of the diagnosis is followed by a second jolt: the high price of cancer drugs.

They are so astronomical that a growing number of patients can’t afford their co-pay, the percentage of their drug bill they have to pay out-of-pocket. As we first reported in October, this has led to a revolt against the drug companies led by some of the most prominent cancer doctors in the country.

Dr. Leonard Saltz: We’re in a situation where a cancer diagnosis is one of the leading causes of personal bankruptcy.

Dr. Leonard Saltz is chief of gastrointestinal oncology at Memorial Sloan Kettering, one of the nation’s premier cancer centers, and he’s a leading expert on colon cancer.

Lesley Stahl: So, are you saying in effect, that we have to start treating the cost of these drugs almost like a side effect from cancer?

Dr. Leonard Saltz: I think that’s a fair way of looking at it. We’re starting to see the term “financial toxicity” being used in the literature. Individual patients are going into bankruptcy trying to deal with these prices.

Lesley Stahl: The general price for a new drug is what?

Dr. Leonard Saltz: They’re priced at well over $100,000 a year.

Lesley Stahl: Wow.

Dr. Leonard Saltz: And remember that many of these drugs, most of them, don’t replace everything else. They get added to it. And if you figure one drug costs $120,000 and the next drug’s not going to cost less, you’re at a quarter-million dollars in drug costs just to get started.

Lesley Stahl: I mean, you’re dealing with people who are desperate.

Dr. Leonard Saltz: I do worry that people’s fear and anxiety are being taken advantage of. And yes, it costs money to develop these drugs, but I do think the price is too high.

The drug companies say it costs over a billion dollars to bring a new drug to market, so the prices reflect the cost of innovation.

The companies do provide financial assistance to some patients, but most people aren’t eligible. So many in the middle class struggle to meet the cost of their co-payments. Sometimes they take half-doses of the drug to save money. Or delay getting their prescriptions refilled.

Dr. Saltz’s battle against the cost of cancer drugs started in 2012 when the FDA approved Zaltrap for treating advanced colon cancer. Saltz compared the clinical trial results of Zaltrap to those of another drug already on the market, Avastin. He says both target the same patient population, work essentially in the same way. And, when given as part of chemotherapy, deliver the identical result: extending median survival by 1.4 months, or 42 days.

Dr. Leonard Saltz: They looked to be about the same. To me, it looked like a Coke and Pepsi sort of thing.

Then Saltz, as head of the hospital’s pharmacy committee, discovered how much it would cost: roughly $11,000 per month, more than twice that of Avastin.

Lesley Stahl: So $5,000 versus $11,000. That’s quite a jump. Did it have fewer side effects? Was it less toxic? Did it have…

Dr. Leonard Saltz: No…

Lesley Stahl: …Something that would have explained this double price?

Dr. Leonard Saltz: If anything, it looked like there might be a little more toxicity in the Zaltrap study.

Lesley Stahl: So Zaltrap. One day your phone rings and it’s Dr. Saltz. Do you remember what he said?

Dr. Peter Bach: He said, “Peter, I think we’re not going to include a new cancer drug because it costs too much.”

Lesley Stahl: Had you ever heard a line like that before?

Dr. Peter Bach: No. My response was, “I’ll be right down.”

Lesley Stahl: You ran down.

Dr. Peter Bach: I think I took the elevator. But yes, exactly.

Bach determined that since patients would have to take Zaltrap for several months, the price tag for 42 days of extra life would run to nearly $60,000. What they then decided to do was unprecedented: reject a drug just because of its price.

Dr. Peter Bach: We did it for one reason. Because we need to take into account the financial consequences of the decisions that we make for our patients. Patients in Medicare would pay more than $2,000 a month themselves, out-of-pocket, for Zaltrap. And that that was the same as the typical income every month for a patient in Medicare.

Lesley Stahl: The co-pay.

Dr. Peter Bach: Right. 20 percent. Taking money from their children’s inheritance, from the money they’ve saved. We couldn’t in good conscience say, “We’re going to prescribe this more expensive drug.”

And then they trumpeted their decision in the New York Times. Blasting what they called “runaway cancer drug prices,” it was a shot across the bow of the pharmaceutical industry and Congress for passing laws that Bach says allow the drug companies to charge whatever they want for cancer medications.

Dr. Peter Bach: Medicare has to pay exactly what the drug company charges. Whatever that number is.

Lesley Stahl: Wait a minute, this is a law?

Dr. Peter Bach: Yes.

Lesley Stahl: And there’s no negotiating whatsoever with Medicare?

Dr. Peter Bach: No.

Another reason drug prices are so expensive is that according to an independent study, the single biggest source of income for private practice oncologists is the commission they make from cancer drugs. They’re the ones who buy them wholesale from the pharmaceutical companies, and sell them retail to their patients. The mark-up for Medicare patients is guaranteed by law: the average in the case of Zaltrap was six percent.

Dr. Leonard Saltz: What that does is create a very substantial incentive to use a more expensive drug, because if you’re getting six percent of $10, that’s nothing. If you’re getting six percent of $10,000 that starts to add up. So now you have a real conflict of interest.

But it all starts with the drug companies setting the price.

Dr. Peter Bach: We have a pricing system for drugs which is completely dictated by the people who are making the drugs.

Lesley Stahl: How do you think they’re deciding the price?

Dr. Peter Bach: It’s corporate chutzpah.

Lesley Stahl: We’ll just raise the price, period.

Dr. Peter Bach: Just a question of how brave they are and how little they want to end up in the New York Times or on 60 Minutes.

That’s because media exposure, he says, works. Right after their editorial was published, the drug’s manufacturer, Sanofi, cut the price of Zaltrap by more than half.

Dr. Peter Bach: It was a shocking event. Because it was irrefutable evidence that the price was a fiction. All of those arguments that we’ve heard for decades, “We have to charge the price we charge. We have to recoup our money. We’re good for society. Trust us. We’ll set the right price.” One op-ed in the New York Times from one hospital and they said, “Oh, okay, we’ll charge a different price.” It was like we were in a Turkish bazaar.

Lesley Stahl: What do you mean?

Dr. Peter Bach: They said, “This carpet is $500” and you say, “I’ll give you $100.” And the guy says, “Okay.” They set it up to make it highly profitable for doctors to go for Zaltrap instead of Avastin. It was crazy!

But he says it got even crazier when Sanofi explained the way they were changing the price.

Dr. Peter Bach: They lowered it in a way that doctors could get the drug for less. But patients were still paying as if it was high-priced.

Lesley Stahl: Oh, come on.

Dr. Peter Bach: They said to the doctor, “Buy Zaltrap from us for $11,000 and we’ll send you a check for $6,000.” Then you give it to your patient and you get to bill the patient’s insurance company as if it cost $11,000. So it made it extremely profitable for the doctors. They could basically double their money if they use Zaltrap.

“High cancer drug prices are harming patients because either you come up with the money, or you die.”

All this is accepted industry practice. After about six months, once Medicare and private insurers became aware of the doctor’s discount, the price was cut in half for everyone.

John Castellani: The drug companies have to put a price on a medicine that reflects the cost of developing them, which is very expensive and takes a long period of time, and the value that it can provide.

John Castellani is president and CEO of PhRMA, the drug industry’s trade and lobbying group in Washington.

Lesley Stahl: If you are taking a drug that’s no better than another drug already on the market and charging twice as much, and everybody thought the original drug was too much…

John Castellani: We don’t set the prices on what the patient pays. What a patient pays is determined by his or her insurance.

Lesley Stahl: Are you saying that the pharmaceutical company’s not to blame for how much the patient is paying? You’re saying it’s the insurance company?

John Castellani: I’m saying the insurance model makes the medicine seem artificially expensive for the patient.

He’s talking about the high co-pay for cancer drugs. If you’re on Medicare, you pay 20 percent.

Lesley Stahl: Twenty percent of $11,000 a month is a heck of a lot more than 20 percent of $5,000 a month.

John Castellani: But why should it be 20 percent instead of five percent?

Lesley Stahl: Why should it be $11,000 a month?

John Castellani: Because the cost of developing these therapies is so expensive.

Lesley Stahl: Then why did Sanofi cut it in half when they got some bad publicity?

John Castellani: I can’t respond to a specific company.

Sanofi declined our request for an interview, but said in this email that they lowered the price of Zaltrap after listening “to early feedback from the oncology community and … To ensure affordable choices for patients…”

Dr. Hagop Kantarjian: High cancer drug prices are harming patients because either you come up with the money, or you die.

Hagop Kantarjian chairs the department of leukemia at MD Anderson in Houston. Inspired by the doctors at Sloan Kettering, he enlisted 119 of the world’s leading leukemia specialists to co-sign this article about the high price of drugs that don’t just add a few weeks of life, but actually add years, like Gleevec.

It treats CML, one of the most common types of blood cancer that used to be a death sentence, but with Gleevec most patients survive for 10 years or more.

Dr. Hagop Kantarjian: This is probably the best drug we ever developed in cancer.

Lesley Stahl: In all cancers?

Dr. Hagop Kantarjian: So far. And that shows the dilemma, because here you have a drug that makes people live their normal life. But in order to live normally, they are enslaved by the cost of the drug. They have to pay every year.

Lesley Stahl: You have to stay on it. You have to keep taking it.

Dr. Hagop Kantarjian: You have to stay on it indefinitely.

Gleevec is the top selling drug for industry giant Novartis, bringing in more than $4 billion a year in sales. $35 billion since the drug came to market. There are now several other drugs like it. So, you’d think with the competition, the price of Gleevec would have come down.

Dr. Hagop Kantarjian: And yet, the price of the drug tripled from $28,000 a year in 2001 to $92,000 a year in 2012.

Lesley Stahl: Are you saying that the drug companies are raising the prices on their older drugs.

Dr. Hagop Kantarjian: That’s correct.

Lesley Stahl: Not just the new ones. So you have a new drug that might come out at a $100,000, but they are also saying the old drugs have to come up to that price, too?

When we asked Novartis why they tripled the price of Gleevec, they told us, “Gleevec has been a life-changing medicine … When setting the prices of our medicines we consider … the benefits they bring to patients … The price of existing treatments and the investments needed to continue to innovate…”

[Dr. Hagop Kantarjian: This is quite an expensive medication.]

Dr. Kantarjian says one thing that has to change is the law that prevents Medicare from negotiating for lower prices.

Dr. Hagop Kantarjian: This is unique to the United States. If you look anywhere in the world, there are negotiations. Either by the government or by different regulatory bodies to regulate the price of the drug. And this is why the prices are 50 percent to 80 percent lower anywhere in the world compared to the United States.

Lesley Stahl: Fifty percent to 80 percent?

Dr. Hagop Kantarjian: Fifty percent to 80 percent.

Lesley Stahl: The same drug?

Dr. Hagop Kantarjian: Same drug. American patients end up paying two to three times more for the same drug compared to Canadians or Europeans or Australians and others.

Lesley Stahl: Now, Novartis, which makes Gleevec, says that the price is fair because this is a miracle drug. It really works.

Dr. Hagop Kantarjian: The only drug that works is a drug that a patient can afford.

The challenge, Dr. Saltz at Sloan Kettering says, is knowing where to draw the line between how long a drug extends life and how much it costs.

Lesley Stahl: Where is that line?

Dr. Leonard Saltz: I don’t know where that line is, but we as a society have been unwilling to discuss this topic and, as a result, the only people that are setting the line are the people that are selling the drugs.

Since we first broadcast our story, President Obama asked Congress to change the law and allow Medicare to negotiate prices with drug manufacturers. Few believe, however, that Congress will let that happen anytime soon.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Oral tongue squamous cell carcinoma (OTSCC) is still associated with a poor prognosis due to local recurrence and metastasis. Cancer-associated fibroblasts (CAFs) play an important role in the complex processes of cancer stroma interaction and tumorigenesis.

This study aims to determine the role of CAFs in the development and progression of OTSCC.

Methods: Immunohistochemistry was performed to evaluate the frequency and distribution of CAFs in 178 paraffin specimens from patients with OTSCC. Immunofluorescence, a cell proliferation assay, flow cytometry, migration and invasion assays and western blot analysis were used to study the effects of CAFs and the corresponding conditioned medium (CM) on the proliferation and invasion of OTSCC cell lines.

Another prognostic tool may be in the offing for clinicians to use in evaluating patients with oropharyngeal cancers, new research suggests.

The presence in serum of three antibodies to human papillomavirus type 16 (HPV16) was predictive of better progression-free and overall survival in these patients, according to Kristina R. Dahlstrom, PhD, from the University of Texas MD Anderson Cancer Center, in Houston, and colleagues.

Patients whose serum was positive for the presence of three specific antibodies to “early” (E) proteins involved in replication and growth of HPV16 had dramatically better rates of overall survival (OS) and progression-free survival (PFS) compared with patients whose serum was negative for the antibodies, they reported online June 15 in Clinical Cancer Research.

Specifically, for those patients whose serum was positive for any E antibodies, 5-year estimated OS was 87.4%, compared with 42.2% for patients whose sereum was negative for all E antibodies (P < .001). The respective 5-year PFS rates were 82.9% and 46.1% (P < .001).

“These results hint at a prognostic stratification of patients with HPV-related oropharynx cancer reflecting humoral immune response to HPV type 16 E proteins and thus may help in choosing immunotherapy approaches for such patients in future,” said senior author Erich M. Sturgis, MD, MPH, a surgeon at MD Anderson, in comments to Medscape Medical News.

Currently, the serology results are not strong enough to be used as clinical decision tools for choosing current therapies, she added.

Their findings also suggest that vaccine-based immunotherapy targeted against HPV16 E-antigens combined with other immunotherapies such as checkpoint inhibitors might be effective against recurrent or metastatic HPV16-positive cancers of the oral cavity and pharynx, said Dr Sturgis.

The findings appear to further illuminate what is going on immunologically in these patients, said an expert not involved with the research.

“This is certainly an interesting study that builds upon our early understanding of the role of the host’s immune response in determining outcomes in HPV-associated oropharynx cancers,” commented Lori J Wirth, MD, a head and neck cancer specialist at the Massachusetts General Hospital Cancer Center, in Boston.

“We know from responses experienced by HPV-positive oropharyngeal squamous cell carcinoma patients enrolled in early clinical trials investigating checkpoint inhibitors that the host immune system can be exploited for a therapeutic end. The more we know about the host immune response to this virally mediated cancer, the better we’ll get at taking advantage of it,” she told Medscape Medical News.

More Cancers, Better Outcomes

Earlier studies have shown that although the incidence of HPV-related head and neck cancers is rising, patients with oropharyngeal squamous cell carcinomas positive for HPV16 have significantly better prognoses than patients with the same cancers not related to HPV infections.

To see whether they could identify prognostic biomarkers in patients with HPV-related oropharyngeal cancers, the investigators used enzyme-linked immunosorbent assasy to quantify immunoglobulin G antibodies to both early antigens (E1 and E4-E7) to the viral capsid proteins L1 and L2, and to the N-terminal and C-terminal fragments of E2 (NE2, CE2).

Among serum samples taken from 209 patients with oropharyngeal cancers at diagnosis, at the end of treatment, and during follow-up, PFS was significantly better for patients testing positive for any E antigen (P < .001), but not for patients testing positive for any L antigen. Therefore, for all subsequent analyses, the investigators focused only on patients testing positive for E antigens.

In multivariable models adjusted for age, smoking status, and treatment, the hazard ratio (HR) for death for patients with any E antibodies was 0.20 (95% confidence interval [CI], 0.1 – 0.4).

The HR for progression for those with any E antibodies was 0.20; (95% CI, 0.1 – 0.5).

The investigators also found that serum positivity for NE2, E1, and E6 were were all strongly associated with better OS and PFS, with respective HRs of 0.20, 0.30, and 0.30 (all significant, as shown by 95% CI).

“Specific antibody status has the potential to be a useful prognostic indicator that may identify subsets of patients diagnosed with HPV16-positive tumors who may benefit from altered monitoring and/or treatments. In addition, the suggestion that immune response to HPV16 antigens is important to cancer outcomes suggests the potential of augmenting immune responses to improve treatment of patients with HPV-driven oropharyngeal carcinoma,” the investigators write.

The study was supported by grants from the National Institutes of Health. Dr Sturgis and Dr Wirth have reported no relevant financial relationships.

The number of oral cancer deaths related to tobacco use is on the rise nationwide according to the Oral Cancer Foundation. Brian Hill is the founder of the OCF and a survivor of the disease.

Cody Kiser encourages the youth to not start using tobacco to help secure good health. Oral Cancer Foundation

“Up until about (the year) 2000 this was primarily a disease of older men who had smoked a lot or chewed tobacco during their lifetime,” Hill said. “About that point in time we started to see a shift in the cause of the disease.”

Hill said tobacco is still a primary cause of oral cancers and adds that the oral human papillomavirus type 16 (HPV16) is new etiology that has forced the number of cases to accelerate.

According to an October 2014 study by Johns Hopkins researchers the HPV16 causes cancers of the mouth and throat and that any form of tobacco use increases the risk of the virus. The research suggests as few as three cigarettes a day can increase the risk of infection by almost one-third.

Hill created the foundation in 1999 to promote change by educating the public about risk factors that contribute to the disease. Among those risks is the use of spit tobacco.

“The world of rodeo has been the realm of sponsorship by the tobacco industry for decades,” Hill said. “With the nicotine content in a can of dip equaling approximately that of 80 cigarettes, this addiction can be one of the hardest to break. We hope to educate parents and youth about the dangers before they even get started.”

The OCF is turning to professional rodeo competitors to serve as positive role models during a national campaign.

Cody Kiser is a professional bareback bronc rider from Reno, Nevada. He was in Delta, Utah recently where he competed at the Millard County Fairgrounds. Kiser told parents at the rodeo that nearly 15 percent of high school boys in the United States use smokeless tobacco.

“My dad was a cowboy, so I know what it’s like looking up to cowboys as heroes for my whole life. Health and fitness have always been incredibly important to my family. My dad was a positive role model in my life growing up in that regard, and the idea of using spit tobacco never appealed to me,” Kiser said. “Right now, I’m pursuing rodeo as a passion of mine, and if at the same time I can do some good in the world and set the right example for young kids who might look up to me, then I’m honored and eager to do so.”

Kiser said cowboys have a reputation that is second only to baseball players for being users of tobacco in the world of sports. He wants to change that reputation throughout the country and in Utah, where rodeo is popular.

“From my point of view, Utah seems to be on the front lines of health and fitness,” he said. “I’ve been very impressed with Utah as far as a healthy lifestyle, people who don’t smoke and chew so it’s good to see in Utah that they don’t do that as much.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

A single dose of a vaccine against human papillomavirus (HPV) may prevent cervical cancer as effectively as the standard three-dose regimen, researchers concluded after analyzing the combined results of two large vaccine trials. The HPV vaccine in these studies was Cervarix (GlaxoSmithKline), which is effective against HPV strains 16/18.

If randomized controlled trials ultimately support the result of this post hoc analysis, it could broaden protection against cervical cancer in areas of the world where vaccination programs are hardest to administer and where cervical cancer is disproportionately burdensome, the study authors say.

“Even if you ignore the expense, the feasibility of implementing and getting back to individuals for a second and third dose is quite challenging, especially in places where there is no infrastructure,” coauthor Cosette Wheeler, PhD, Regents Professor, Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center in Albuquerque, told Medscape Medical News.

The possibility of a single-dose HPV vaccine is “a huge public health win,” coauthor Aimée R. Kreimer, PhD, Investigator, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, told Medscape Medical News. “Even if one dose protects only against HPV types included in the vaccine formulation, if we vaccinated most girls, we would have the chance to reduce cervical cancer by around 75%.”

That’s the exciting part, Dr Wheeler added. “If we’re able to achieve success with one dose, or frankly even with two doses, that makes the possibility for worldwide prevention much greater.”

HPV type 16 is the leading cause of cervical cancer, responsible for about 50% of all cases, and HPV 18 is the second-largest cause, at 20%.The authors note that this research was carried out with Cervarix, and it is unclear whether the results would also apply to the other HPV vaccine that is available, Gardasil (Merck & Co.), which is active against several more HPV strains and is the product that is commonly used in the United States. Whether results of this trial have any bearing on Gardasil will depend on what’s driving the strong immune response to Cervarix, the authors suggest. Cervarix carries a proprietary adjuvant, which may be responsible for the immune response.

Surprise Over Efficacy Findings

The idea of the current post hoc analysis arose from results in the large randomized controlled Costa Rica Vaccine Trial, in which about 20% of participants received fewer than three doses of HPV-16/18 vaccine. “We were surprised to observe that efficacy was the same regardless of the number of doses received,” Dr Kreimer told Medscape Medical News.

That led to the post hoc analysis of the immunization results from the Costa Rica Vaccine Trial combined with results from the only other large phase 3, double-blind, randomized trial of HPV-16/18, for a total of more than 14,000 participants, ages 15 to 25 years, including about 7000 control subjects. The second trial, called PATRICIA (Papilloma Trial Against Cancer in Young Adults), took place in 14 countries. The analysis found that 4 years after vaccination, women who received the required three vaccine doses and women who received fewer than three doses — usually due to pregnancy or a colposcopy referral — were equally protected against HPV-16/18. Further, the analysis showed a potential benefit of cross-protection against closely related HPV strains 31/35/45 among women whose two doses were 6 months apart — a benefit previously seen only with three doses.

Four-year vaccine efficacy against HPV-16/18 in the combined analysis was 77% for the 13,296 (6634 case, 6662 control) women in the three-dose group, 76% for the 549 (273 case, 276 control) women in the two-dose group, and 85.7% for the 238 (138 case, 100 control) women in the single-dose group. Efficacy against the closely related HPV-31/33/35 was 59.7% for three doses, 37.7% for two doses, and 36.6% for one dose. When data for the two doses were analyzed according to dosing regimen, the cross-protective efficacy was 10.1% for those who received their second dose 1 month after the first and 68.1% for those who received the second dose at 6 months.

Antibody concentrations for two doses given 6 months apart were very close to concentrations for three doses, the research showed. One-dose vaccination titers at 6 to 48 months were lower than those for two or three doses, “but the titers were stable and several times higher than those identified for natural immunity,” the researchers write. “We can now infer that these lower, vaccine-induced antibody titers provide as strong HPV prevention as the titers from two or three doses, at least in the short term.”

Just how long these vaccines will provide protection still needs to be determined. “We know with three doses we can see the protection going out toward 10 years, and we hope that maybe the protection is lifelong,” commented Dr Wheeler. “That does not mean that we know we will never need a booster. And that doesn’t mean if we give less than three doses that we know about the longevity or durability of that protection. So that’s another piece of the puzzle.”

Although these results cannot be applied to Gardasil, Dr Wheeler notes that studies looking at Gardisil antibody titers after two doses look promising.

In an accompanying comment, Julia M.L. Brotherton, Medical Director, National HPV Vaccination Program Register, VCS Registries, East Melbourne, Victoria, Australia, commented: “These data suggest that one dose of bivalent HPV vaccine might be adequate to protect against HPV-16 and HPV-18 persistent infections and, therefore, probably disease. HPV-16 and HPV-18 cause more than 70% of cervical cancers and the vast majority of HPV-related cancers at other anatomic sites. If this finding is confirmed, it opens up a great opportunity to extend the reach of protection using HPV vaccines to more people than we would have previously thought possible.”

Four authors of the study are GSK employees and own shares and stock options in the company. Other researchers had financial or advisory relationships GSK, Roche Molecular Systems, Merck, and Sanofi Pasteur MSD. Dr Brotherton notes that she has been an investigator for investigator-initiated HPV epidemiology research grants partially funded by bioCSL/Merck, but this did not involve financial compensation.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Utility player Mark DeRosa loads a wad of smokeless tobacco while playing for the San Francisco Giants before a game against the Dodgers on March 31, 2011. The use of smokeless tobacco is prevalent in the major leagues. (Kevork Djansezian / Getty Images)

Rick Vanderhook played for Cal State Fullerton’s 1984 College World Series championship team and was a Titans assistant when they won two more. So he remembers the days when cans and pouches of smokeless tobacco were omnipresent in the uniform pockets of the participants.

Not anymore. The NCAA banned tobacco use on the field in the early 1990s.

“It’s probably cut back, I’ll say, almost 90% compared to what it was 25 years ago,” said Vanderhook, who in his fourth season as head coach has guided the Titans back to Omaha, where they will open against defending national champion Vanderbilt on Sunday at 5 p.m.

Smokeless tobacco remains ingrained in baseball culture, however, including the college and high school levels where it is banned.

“It sounds bad, but it’s part of the game,” said Fullerton pitcher Thomas Eshelman, echoing nearly every coach and player interviewed for this article.

Minor league players can be fined for having tobacco products in their locker or partaking on the field. Major leaguers are prohibited from using tobacco during televised interviews and player appearances, and they cannot carry tobacco products in their uniforms. But they are otherwise not prohibited from using it on the field.

Before he died of salivary gland cancer last year, baseball Hall of Famer Tony Gwynn said he believed his habit of using smokeless tobacco caused the disease that took his life at age 54.

Curt Schilling, a former All-Star pitcher, said last year he had undergone treatment for cancer that resulted from smokeless tobacco use. In April, he penned an open letter to his younger self warning of the dangers.

And last month, the mayor of San Francisco signed an ordinance that in 2016 will ban tobacco from all sporting venues in the city, including AT&T Park, home of the defending World Series champion San Francisco Giants.

That has not stopped many college players from using smokeless tobacco.

“No matter how many times you look a guy in the eye and say Tony Gwynn and Curt Schilling, if that guy wants to dip, he’s going to find a way,” said Andy Lopez, who guided Pepperdine and Arizona to national titles before retiring last month after 33 years as a college coach.

The NCAA prohibits players, coaches, umpires, athletic trainers and managers from using tobacco at game sites. If umpires catch players using tobacco, the player and coach face ejection.

“There is zero tolerance,” said Chuck Lyon, a college umpire for nearly three decades.

According to the NCAA rule book, “umpires who use tobacco before, during or after a game in the vicinity of the site shall be reported to and punished by the proper disciplinary authority.”

A tin of chewing tobacco is seen tucked into the glove of Dodgers reliever Chris Hatcher when he was playing wiht the Miami Marlins last season. (Wilfredo Lee / Associated Press)

Players and coaches interviewed for this story said they had seen umpires using tobacco. But Lyon said, “as a crew chief, I would turn that in immediately.”

Results of the NCAA’s most recent quadrennial survey of about 21,000 college athletes from all sports showed that tobacco use by college baseball players was decreasing. The 2013 results, released last July in a report titled, “NCAA National Study of Substance Abuse Habits of College Student-Athletes,” showed a drop in “spit” tobacco use since 2009.

In 2005, the overall percentage of acknowledged use in the previous 12 months was 42.5%. It climbed to 52.3% in 2009, but dropped to 47.2% in 2013 — though that’s still nearly half of the players in a sport in which it is banned.

Coaches said they address tobacco with their players before every season.

“You also bring it up throughout the season,” UCLA Coach John Savage said, “but it’s not a daily reminder.”

Cal State Northridge Coach Greg Moore said, “We educate them constantly and talk about their choices.” But, he added, “I know that me saying smokeless tobacco is unhealthy is not going to get a guy to change his habit.”

The California Interscholastic Federation, which governs high school sports in the state, forbids the use of tobacco products by athletes and coaches. But most players say they first experimented with tobacco in high school.

“They get into it for the same reason 12-year-olds start smoking — they think it’s a cool thing to do,” UC Irvine Coach Mike Gillespie said.

Chatsworth High Coach Tom Meusborn said tobacco use by players has dramatically dissipated since he began coaching at the school in 1990. “I think they understand and are becoming more health conscious with their training and diet,” he said.

Jim Ozella, Newhall Hart’s coach since 2000, also sees fewer high school players using tobacco. “I just bring up the topic of Tony Gwynn,” said Ozella, whose son worked as an equipment manager at San Diego State when Gwynn coached there.

College players said they were aware of the risks of using tobacco products.

Still, Cal State Northridge infielder William Colantono began to dip as a young member of a mostly older varsity high school team. “Being around them, I picked it up,” he said. “Not that I’m proud of it.”

Colantono said that while most of his summer league teammates used smokeless tobacco, only “a handful” of his Northridge teammates do, and they partake off the field.

“It’s easy for me not to have to do it on the field,” he said. “I’m not crazy about it where I have to have it all the time.”

Eshelman, Fullerton’s ace right-hander, started to dip in high school because “I thought it was cool.” Fellow Titans pitcher John Gavin began in high school on “a dare.” Both said they occasionally use tobacco, but not on the field.

“After a game when you want to hang out and relax,” said Eshelman, a junior.

“Just kind of a stress reliever,” said Gavin, a freshman.

Several college baseball summer leagues, which have rosters comprised of players from across the United States, also ban the use of tobacco during games.

Sal Colangelo, longtime manager of the Bethesda (Md.) Big Train in the Cal Ripken Collegiate League, said he attempts to educate players, but for some “it’s a way of life.”

“You go into their trucks and there are cases and cases of tobacco and dip,” he said. “It’s like a 7-Eleven.”

Several coaches from West Coast schools acknowledged using tobacco, though a few agreed to speak about it only if they were not identified.

One, who said he recently quit, recalled an umpire once threatening to eject him for chewing when he went out to argue a call. Another, who has used smokeless tobacco for more than two decades, admitted he was addicted.

“For me, personally, that would be one of my greatest accomplishments if I can stop,” he said.

Former Pepperdine coach Steve Rodriguez played on Pepperdine’s 1992 national championship team and professionally for seven seasons, including 18 games in the major leagues. He coached the Waves for 12 seasons before being hired this week as coach of Baylor. He said he chewed leaf tobacco until about five years ago.

“I was a hypocrite because I would say, ‘You can’t do it,’ but I would still do it,” he said, adding he is now passionate about educating his players about the risks.

“I want to make sure,” he said, “that I give them the best opportunity to not have to deal with really, really big issues.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

The immunotherapy Keytruda (pembrolizumab), in a recent study, proved twice as effective for the treatment of head and neck cancer as Erbitux (cetuximab), the only targeted therapy indicated as a therapy for the disease.

The multisite study offers the largest experience to date of how immunotherapy can be deployed in patients with head and neck cancer, and could change the way the disease is treated. The findings were announced May 29 during the annual meeting of the American Society of Clinical Oncology, a gathering of nearly 30,000 oncology professionals taking place in Chicago.

Keytruda is an antibody designed to disable the protein PD-1 so it cannot do its job of keeping the immune system in check; this allows T cells to become more active in recognizing and fighting cancer cells. In the study, investigators found that the drug produced broad and durable responses in patients with advanced head and neck cancer.

Fifty-six percent of patients in the study experienced some tumor shrinkage with Keytruda, and 86 percent of those patients continued to respond to treatment at data cutoff on March 23, 2015. Keytruda produced an overall response rate (ORR) of 25 percent, and it proved active in both HPV (human papillomavirus)-positive and HPV-negative patients.

“The efficacy was remarkable — pembrolizumab seems to be roughly twice as effective, when measured by response, as our only targeted therapy, cetuximab,” said Tanguy Seiwart, an assistant professor of medicine and associate leader of the head and neck cancer program at the University of Chicago, who presented the results in a press briefing during the ASCO meeting. “We have high hopes that immunotherapy will change the way we treat head and neck cancer.”

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) has a poor prognosis with a median overall survival (OS) of 13 months in patients treated in the first-line setting, and six months in previously treated patients. Previously treated patients made up the majority of the population of the study, which built on earlier findings from the KEYNOTE-012 study (NCT01848834). In that study, Keytruda — administered at 10 mg/kg every two weeks — had a 20 percent response rate in patients with advanced HNSCC whose tumors were positive for the protein PD-L1.

The findings reported May 29 were based on results from an expansion of that first trial, which involved 132 patients with advanced HNSCC who were recruited regardless of their PD-L1 or HPV status. Importantly, said Seiwert, patients in this cohort received a fixed dose of Keytruda (200 mg every three weeks), representing “a very convenient dosing schedule.”

Eligible patients had measureable disease based on RECIST 1.1 response evaluation criteria and an ECOG performance status of 0 or 1. The majority of enrollees were male (83 percent), and 56.8 percent had received two or more lines of therapy for disease recurrence. Radiographic imaging was used to assess tumor response every eight weeks. Patients were treated as long as they didn’t show progression of disease or as long as they demonstrated clinical improvement, Seiwert explained.

“In addition to the 25 percent response rate,” said Seiwert, “about 25 percent also had stable disease, so when we take these together, we have a disease control rate of about 50 percent, which is remarkable in this disease, especially in a heavily pretreated population.”

Moreover, he said, about two-thirds of patients had received two or more prior lines of therapy, which generally is an indicator of a very poor prognosis.

For the 56 percent of patients whose tumors decreased in size, Seiwert said the responses often occurred early at eight or 16 weeks, although there were a few outliers with late responses.

“Importantly, those patients who did respond oftentimes continued to have responses — 86 percent of patients had durable responses in this cohort,” he continued, adding that not only are responders remaining on the therapy, but so are many patients who have stable disease, with a total of 40 patients staying on the drug.

“Overall, and in keeping with what we already know about pembrolizumab, this was a very well-tolerated agent,” said Seiwert, “certainly better tolerated than what we usually see in head and neck cancer with aggressive chemotherapy and radiotherapy.”

Serious side effects were reported in fewer than 10 percent of patients. The most common side effects were fatigue (15.2 percent of patients), hypothyroidism (9.1 percent), and decreased appetite and rash, each occurring in 7.6 percent of patients. Four patients discontinued treatment due to immune-related side effects: two due to grade 2 interstitial lung disease and grade 3 colitis, respectively, and two patients for grade 3 pneumonitis.

Analysis of the findings based on biomarker status is ongoing, and Seiwert is hopeful that with the emergence of new potential biomarkers, researchers will be able to pinpoint which patients with HNSCC are most likely to benefit from the immunotherapy.

For example, another related study that Seiwert and colleagues are reporting at ASCO (abstract 6017) has shown that the expression of the gene signature interferon-gamma in head and neck tumors had a very strong negative predictive value of response to Keytruda. “In the future, these results may help us, if validated, to determine which patients should or should not [be given] pembrolizumab,” Seiwert said.

Pembrolizumab versus standard treatment for HNSCC also is being evaluated in two phase 3 trials that are currently recruiting participants (NCT02252042 and NCT02358031).

Three tobacco giants have been ordered by a Canadian court to pay billions of dollars in moral and punitive damages to nearly 100,000 smokers, in what has been hailed as an “historic judgment” by the plaintiffs in Quebec.

Imperial Tobacco Canada, Rothmans, Benson & Hedges, and JTI-Macdonald were found to have violated their general duty not to cause injury to another, their duty to inform their clients of the risks and dangers of their products, and their obligation not to mislead their clients. A Quebec Superior Court slapped the three cigarette manufacturers — which have already vowed to appeal — with damages totaling CAD $15.5 billion ($12 billion US), to be split among them.

The ruling means that plaintiffs suffering from lung or throat cancer are entitled to receive CAD $80,000 or $100,000 ($63,000 or $80,000), while those afflicted with emphysema can receive CAD $24,000 or $30,000 ($19,000 or $24,000), plus the interest accumulated since 1998, which is when the lawsuit commenced.

“Today marks an important day for the victims of tobacco who have waited almost 17 years for this moment”, said Mario Bujold, executive director of the Quebec Council on Tobacco and Health on Monday.

“By choosing not to inform either the public health authorities or the public directly of what they knew, the Companies chose profits over the health of their customers,” Justice Brian Riordan wrote in his 276-page judgment. “Whatever else can be said about that choice, it is clear that it represent a fault of the most egregious nature and one that must be considered in the context of punitive damages.”

Two class actions were heard as part of the same trial. One, spearheaded by the Council, included 99,957 Quebec smokers and ex-smokers who had developed emphysema, lung cancer, or throat cancer. A second class action was much broader, representing 918,218 people addicted to tobacco in Quebec. While the Quebec Council on Tobacco and Health said the judge sided with the plaintiffs in both cases, only those in the first group will receive compensation.

But Rothmans, Benson & Hedges said the cases are “far from over”, a sentiment shared by the other manufacturers.

“We will vigorously appeal this lower court’s judgment, and believe that we have very strong legal grounds to overturn the judgment in its entirety,” RBH spokeswoman Anne Edwards said in a statement.

She noted that not a single class member, in nearly three years of trial, “showed up to say that he or she was unaware of the risks of smoking,” and said given the “prevailing law and common sense” the judgement should not stand.

JTI-Macdonald Corp. also said it “fundamentally disagrees” with the judgment and intends to file an appeal.

“Since the 1950s, Canadians have had a very high awareness of the health risks of smoking. That awareness has been reinforced by the health warnings printed on every legal cigarette package for more than 40 years,” it said in a statement, adding that the company complies with all Canadian and Quebec laws.

In its statement, Imperial Tobacco Canada called it “astounding to be handed this decision when the federal government has set the standard for the conduct of Imperial Tobacco Canada with which the company has always complied.”

Still, Andre Lesperance, one of the lawyers involved in the case for the plaintiffs, said on Monday that the companies “lied” to their customers and “hurt their right to life,” The Canadian Press reported.

“It’s a great victory for victims as well as for society in general,” he said.